Molecular mechanism of inflammation-induced depression

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670510
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Chiba University
• Principal Investigator: HASHIMOTO KENJI 千葉大学, 社会精神保健教育研究センター, 教授 (10189483)
• Research Collaborator: ZHANG Ji-chun 千葉大学, 社会精神保健教育研究センター, 特任助教 (00733320)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 脳神経疾患 / 炎症 / うつ病 / ニコチン受容体 / 脳由来神経栄養因子

Outline of Final Research Achievements

Although alpha-7 nicotinic acetylcholine receptor (nAchR), a subtype of nicotine receptors, plays a role in the inflammation, the role of alpha-7 nAChR in depression has been unknown. In this study, we examined the role of alpha-7 nAChR in depression using alpha-7 nAChR KO mice. We found that alpha-7 nAChR KO mice show depression-like phenotype, including anhedonia. We also found an increase of brain-derived neurotrophic factor (BDNF) in the nucleus accumbens, but not other regions (prefrontal cortex and hippocampus). Furthermore, TrkB antagonist ANA-12, but not TrkB agonist 7,8-DHF, showed antidepressant-like effects in alpha-7 nAChR KO mice. These findings suggest that increased BDNF-TRkB signaling in the nucleus accumbens, but not other brain regions, plays a key role in depression-like behavior in alpha-7 nAChR KO mice.

Free Research Field

精神医学